• Title/Summary/Keyword: Cascade effect

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Study on the Inhibitory Effect of Anti-Alzheimer in CT105-induced Neuro 2A Cell Lines by Gamiyaungshinhwan Water Extract (가미녕신환(加味寧神丸)이 CT105로 유도된 Neuro2A 세포주에서의 항치매 효과(效果))

  • Bang, Jae-Sun;Yoon, Hyun-Duk;Shin, Oh-Chul;Shin, Yoo-Jung;Park, Chi-Sang
    • The Journal of Internal Korean Medicine
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    • v.27 no.3
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    • pp.603-616
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    • 2006
  • The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.

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Comparative Study of Tip Clearance Loss in Impulse and Reaction Turbine Cascades (충동터빈과 반동터빈 캐스케이드에서의 팁 간극 손실에 대한 비교 연구)

  • Park, Kyung-Wook;Jung, Eun-Hwan;Song, Seung-Jin
    • Proceedings of the Korean Society of Propulsion Engineers Conference
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    • 2008.11a
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    • pp.145-148
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    • 2008
  • Korea Aeronautics Research Institute (KARI) is developing a turbo pump that has 1-stage impulse turbine and relatively high tip clearance for safety. The objective of this research is to investigate the effect of reaction on tip clearance loss in axial turbines. Both cascades were tested in a subsonic wind tunnel. In each cascade, total pressure was measured for tip clearance ranging from 1% to 20% of chord. In results, increasing tip clearance, total pressure loss in reaction turbines is continually increased but impulse turbines keep almost same level of mass averaged total pressure loss. When tip clearance becomes more than 10% of chord, mass-averaged total pressure loss in impulse turbines is less than in reaction. This means that when tip clearance is more than 10% of chord, impulse turbines have better efficiency than reaction turbines.

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Undaria pinnatifida Extracts and Alginic Acid Attenuated Muscle Atrophy in TNF-α Induced Myoblast Cells through MAFbx Signaling Cascade (미역 추출물과 알긴산의 근육손실 억제 효능)

  • Choi, Sang Yoon;Kim, Mina;Lee, Hyun Hee L.;Hur, Jinyoung
    • Journal of Life Science
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    • v.31 no.2
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    • pp.137-143
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    • 2021
  • Muscle atrophy refers to a decrease in muscle cells due to damage to muscle fibers. It is reported that muscle atrophy is caused by heart disease, diabetes, and other chronic diseases related to aging. The purpose of this study is to reveal the inhibitory effects of seaweed extracts, which are widely consumed in Korea, and alginic acid on muscle cell damage in muscle atrophy and regeneration models. We found that seaweed extracts (U) and alginic acid (A) attenuated TNF-α-induced muscle atrophy in differentiated C2C12 myoblast cells and inhibited muscle atrophy markers such as MuRF1 and MAFbx. In addition, U and A also regulated ubiquitination marker FoxO1 protein. To confirm the muscle regeneration effect in animal tissue, cardiotoxin (CTX) was used for the regeneration model. Six hours after CTX injection, gastrocnemius muscle volume was increased compared to control. Otherwise, the muscle volume of the U and A treatment groups was not changed. U and A also upregulated regeneration markers MyHC and PGC-1α in a CTX mouse model. These results indicate that seaweed extracts and alginic acid, a seaweed component, are applicable to senile sarcopenia by inhibiting muscle loss and promoting muscle regeneration.

p-coumaric acid, an active ingredient of Panax ginseng, ameliolates atopic dermatitis-like skin lesions through inhibition of thymic stromal lymphopoietin in mice

  • Moon, Phil-Dong;Han, Na-Ra;Lee, Jin Soo;Kim, Hyung-Min;Jeong, Hyun-Ja
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.176-182
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    • 2021
  • Background: Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. p-coumaric acid (pCA) is an active ingredient of Panax ginseng Meyer (Araliaceae). Methods: Here, we estimated an anti-AD effect of pCA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions. Results: The treatment with pCA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-α, IL-6, and IL-1β in HMC-1 cells. pCA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBα/NF-κB in HMC-1 cells. pCA also decreased the productions of TSLP, TNF-α, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, pCA-treated group alleviated pathological changes of AD-like lesions. pCA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by pCA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-α, IL-6, and IL-4 were suppressed following treatment with pCA. Conclusion: This study suggests that pCA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.

The changes of immune-related molecules within the ileal mucosa of piglets infected with porcine circovirus type 2

  • Shi, Fengyang;Li, Qiuming;Zou, Zhanming;Wang, Yang;Hou, Xiaolin;Zhang, Yonghong;Song, Qinye;Zhou, Shuanghai;Li, Huanrong
    • Journal of Veterinary Science
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    • v.21 no.5
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    • pp.78.1-78.15
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    • 2020
  • Background: Enteritis is one of the most frequently reported symptoms in piglets infected with porcine circovirus type 2 (PCV2), but the immunopathogenesis has not been reported. Objectives: This study examined the effect of a PCV2 infection on the intestinal mucosal immune function through morphological observations and immune-related molecular detection. Methods: Morphological changes within the ileum of piglets during a PCV2 infection were observed. The expression of the related-molecules was analyzed using a gene chip. The immunocyte subsets were analyzed by flow cytometry. The secretory immunoglobulin A (SIgA) content was analyzed by enzyme-linked immunosorbent assay. Results: The PCV2 infection caused ileal villus damage, intestinal epithelial cells exfoliation, and an increase in lymphocytes in the lamina propria at 21 days post-infection. Differentially expressed genes occurred in the defense response, inflammatory response, and the complement and coagulation cascade reactions. Most of them were downregulated significantly at the induction site and upregulated at the effector site. The genes associated with SIgA production were downregulated significantly at the induction site. In contrast, the expression of the Toll-like receptor-related genes was upregulated significantly at the effector site. The frequencies of dendritic cells, B cells, and CD8+T cells were upregulated at the 2 sites. The SIgA content decreased significantly in the ileal mucosa. Conclusions: PCV2 infections can cause damage to the ileum that is associated with changes in immune-related gene expression, immune-related cell subsets, and SIgA production. These findings elucidated the molecular changes in the ileum after a PCV2 infection from the perspective of intestinal mucosal immunity, which provides insights into a further study for PCV2-induced enteritis.

Increasing Returns to Information and Its Application to the Korean Movie Market

  • Kim, Sang-Hoon;Lee, Youseok
    • Asia Marketing Journal
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    • v.15 no.1
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    • pp.43-55
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    • 2013
  • Since movies are experience goods, consumers are easily influenced by other consumers' behavior. For moviegoers, box office rank is the most credible and easily accessible information. Many studies have found that the relationship between a movie's box office rank and its revenue departs from the Pareto distribution, and this phenomenon has been named "increasing returns to information." The primary objective of the current research is to apply the empirical model proposed by De Vany and Walls (1996) to the Korean movie market in order to examine whether the same phenomenon prevails in the Korean movie market. The other purpose of the present study is to provide managers with useful implications about the release timing of a movie by finding different curvatures that depend upon seasonality. The empirical test on the Korean movie market shows similar results as prior studies conducted on the U.S., Hong Kong, and U.K. movie markets. The phenomenon of increasing returns is generated by information transmission among consumers, which makes some movies become blockbusters and others bombs. The proposed model can also be interpreted in such a way that a change in the rank has a nonlinear effect on the movie's performance. If a movie climbs up the chart, it would be rewarded more than its proportion. On the other hand, if a movie falls down in the ranks, its performance would drop rapidly. The research result also indicates that the phenomenon of increasing returns occurs differently depending on when the movies are released. Since the tendency of the increasing returns to information is stronger during the peak seasons, movie marketers should decide upon the release timing of a movie based on its competitiveness. If a movie has substantial potential to incur positive word-of-mouth, it would be more reasonable to release the movie during the peak season to enjoy increasing returns. Otherwise, a movie should be released during the low season to minimize the risk of being dropped from the chart.

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Network pharmacology analysis of Jakyakgamchotang with corydalis tuber for anti-inflammation (작약감초탕 가 현호색의 항염증 기전에 대한 네트워크 약리학적 분석)

  • Young-Sik Kim;Hongjun Kim;Han-bin Park;Seungho Lee
    • Herbal Formula Science
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    • v.32 no.1
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    • pp.39-49
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    • 2024
  • Objectives : The purpose of this study was to investigate the molecular targets and pathways of anti-inflammatory effects of Jakyakgamchotang with corydalis tuber (JC) using network pharmacology. Methods : The compounds in constituent herbal medicines of JC were searched in TCM systems pharmacology (TCMSP). Target gene informations of the components were collected using chemical-target interactions database provided by Pubchem. Afterwards, network analysis between compounds and inflammation-related target genes was performed using cytoscape. Go enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on inflammation-related targets using DAVID database. Results : 70 active compounds related to inflammation were identified, and 295 target genes related to the anti-inflammatory activity of the compound of JC were identified. In the Go biological process DB and KEGG pathway DB, "inflammatory response", "cellular response to lipopolysaccharide", "positive regulation of interleukin-6 production", and "positive regulation of protein kinase B. signaling", "positive regulation of ERK1 and ERK2 cascade", "positive regulation of I-kappaB kinase/NF-kappaB signaling", "negative regulation of apoptotic process", and "PI3K-Akt signaling pathway" were found to be mechanisms related to the anti-inflammatory effects related to the target genes of JC. The main compounds predicted to be involved in the anti-inflammatory effect of JC were quercetin, licochalcone B, (+)-catechin, kaempferol, and emodin. Conclusions : This study provides the molecular targets and potential pathways of JC on inflammation. It can be used as a basic data for using JC for various inflammatory disease in traditional korean medicine clinic.

Apoptosis of Human Jurkat T Cells Induced by the Methylene Chloride Extract from the Stems of Zanthoxylum schinifolium is Associated with Intrinsic Mitochondria-Dependent Activation of Caspase Pathway (인체 급성백혈병 Jurkat T 세포에 있어서 Zanthoxylum schinifolium 줄기의 methylene chloride 추출물에 의해 유도되는 세포자살기전 규명)

  • Jun, Do-Youn;Woo, Mi-Hee;Park, Hae-Sun;Kim, Jun-Seok;Rhee, In-Koo;Kim, Young-Ho
    • Journal of Life Science
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    • v.18 no.11
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    • pp.1499-1506
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    • 2008
  • To examine antitumor activity of the edible plant Zanthoxylum schinifolium, the cytotoxic effect of various organic solvent extracts of its stems on human acute leukemia Jurkat T cells was investigated. Among these extracts such as methanol extract (SS-7), methylene chloride extract (SS-8), ethyl acetate extract (SS-9), n-butanol extract (SS-10), and residual fraction (SL-11), SS-8 exhibited the most cytotoxic activity against Jurkat T cells. The methylene chloride extract (SS-8) possessed the apoptogenic activity capable of inducing sub-G1 peak along with apoptotic DNA fragmentation in Jurkat T cells. Western blot analysis revealed that SS-8 induced apoptosis via mitochondrial cytochrome c release into cytoplasm, subsequent activation of caspase-9 and caspase-3, and cleavage of PARP, which could be blocked by overexpression of Bcl-xL. Jurkat T cell clone I2.1 $FADD^{-/-}$) and Jurkat T cell clone I9.2 (caspase-$8^{-/-}$ were as sensitive as was the wild-type Jurkat T cell clone A3 to the cytotoxic effect of SS-8, suggesting no contribution of Fas/FasL system to the SS-8-mediated apoptosis. The GC-MS analysis of SS-8 showed that it was composed of 16 ingredients including 9,12-octadecanoic acid (18.62%), 2,4-dihydro-5-methyl-4- (1-methylethylidene)- 2-(4-nitrophenyl)-3H- pyrazol-3-one (14.97%), hexadecanoic acid (14.23%), (z,z)-6,9-pentadecadien- 1-ol (13.73%), 5,6-dimethoxy-2-methyl benzofuran (10.95%), and 4-methoxy-2-methylcinnamic acid (5.38%). These results demonstrate that the methylene chloride extract of the stems of Z. schinifolium can induce apoptotic cell death in Jurkat T cells via intrinsic mitochondria-dependent caspase cascade regulated by Bcl-xL without involvement of the Fas/FasL system.

Apoptotic Effect of Proso Millet Grains on Human Breast Cancer MDA-MB-231Cells Is Exerted by Activation of BAK and BAX, and Mitochondrial Damage-mediated Caspase Cascade Activation (기장 종자 유래 추출물의 인간 유방암 MDA-MB-231 세포에 대한 세포독성에 관련된 미토콘드리아 손상-의존적 아폽토시스 유도 효과)

  • Do Youn Jun;Cho Rong Han;Young Ho Kim
    • Journal of Life Science
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    • v.33 no.1
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    • pp.15-24
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    • 2023
  • To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.

Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene-induced Lung Cancer in Rats Through the Molecular Pathway of Caspase-3-mediated Apoptosis Induction -Anti-lung cancer potential of Condurango 30C in rats-

  • Sikdar, Sourav;Mukherjee, Avinaba;Bishayee, Kausik;Paul, Avijit;Saha, Santu Kumar;Ghosh, Samrat;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.16 no.3
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    • pp.11-22
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    • 2013
  • Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP) in white rats (Rattus norvegicus). Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one ($5^{th}$), two ($5^{th}-6^{th}$) and three ($5^{th}-7^{th}$) months, respectively, and were sacrificed at the corresponding time-points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM), annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two-month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR) expression, a hallmark of lung cancer. Conclusion: The overall result validated a positive effect of Condurango 30C in ameliorating lung cancer through caspase-3-mediated apoptosis induction and EGFR down-regulation.